The purpose of this request is to gain continued support for the present effort to localize, isolate and characterize, immunologically and chemically, embryonic antigens of rodents. Completed work has eliminated Forssman, organ and blood group antigens or casual isoantigens as true fetal antigens shared among specific tumors. Fetal antigens have been isolated in soluble form from fetal and tumor cells. New methods have been developed which should permit meaningful immunochemical characterization of embryonic antigens and provide the desired description of their biological role in development and in malignant processes. The workscope given in the proposal is part of a continuing basic research effort to understand fetal antigen expression in tumors and in the developing fetuses of syngeneic rodents. Embryonic antigens are "autoantigens" transiently expressed in the cells of metazoan embryos. These antigenic determinants in embryo cells elicit maternal immunologic responses (immunoglobulins and T lymphocytes) but the embryo or developing fetus survives these anti-embryo responses under normal conditions. The embryonic antigens which we have studied elicit transplantation rejection-like reactions in the mother. They are uniformly phase specific antigens and are generally not expressed in adult tissues except in neoplasms or in certain autoimmune diseases. Embryonic antigens are shared between many species including mouse and man. Tumors of all metazoans tested carry embryonic antigens. The expression of embryonic determinants now seems to be a uniform characteristic of tumor cells. These antigens are produced in greater quantities by highly malignant cells than by cells with lower metastatic tendencies. Fetal autoantigens on tumor cells elicit a complex array of autochthonous immunologic responses in the host which are not yet clearly defined nor understood. Such investigations are the basis for this grant project.